8-iso-prostaglandin-F2α: a possible trigger or accelerator of diabetic retinopathy

Diabetes mellitus (DM) is a global disease, the number of patients of which is predicted to rise to about 380 million by 2025 by the World Health Organization (WHO)[1]. Diabetic retinopathy (DR) is one of the most sigificant complications in DM[1], and the first cause of irreversible blindness of adults in the world[2]. It occurs in 90% of patients after 20-30y from the diagnosis of DM[1], and about 5 million individuals have DR, which is responsible for approximately 5% of blindness worldwide[3]. There are two main stages of DR: proliferative DR (PDR) and non-PDR (NPDR) [2]. The hallmark of the presence of PDR is neovascularization, while no neovascularization means NPDR[4]. About 60% of diabetic patients suffer from PDR, which is the advanced form of DR[1]. Oxidative stress is defined as the increased generation of free radicals and impaired antioxidant defense which induces imbalance[5]. Because it activates other pathway (e.g. polyol pathway flux, and activation of diacylglyceol-protein kinase C pathway, etc.) and leads to other structural and functional changes, it plays a leading role in the progression of DM and its complications[6]. Oxidative stress can be measured by many indicative parameters, such as lipoperoxidation, protein oxidation, and changes in antioxidant defence system status[7]. Lipid peroxidation biomarkers included malondialdehyde, lipoperoxides and lipid hydroperoxides[7]. However, 8-iso-prostaglandin-F2α (8-iso-PGF2α), as one of the stable products of non-cyclooxygenase peroxidation of arachidonic acid, has proved to be the most available and reliable marker of lipid peroxidation in vivo[8]–[9], and it appears more sensitive and specific than other markers of oxidative stress[8]. Furthermore, 8-iso-PGF2α induces vasoconstriction, mitogenesis and persistent platelet activation[9]–[10], which can contribute to the progression of diabetes and/or its complications. Some previous studies showed that the concentration of 8-iso-PGF2α is associated with the level of acute and chronic glucose fluctuation[11]–[12], the level of hemoglobin A1c (HbA1c), and fasting glucose[13], which might lead to the onset and/or progression of DR. To the best of our knowledge, however, there has been no studies about the relationship between the level of plasma 8-iso-PGF2α and the onset and/or progression of DR so far.